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Science 15 April 1994:
Vol. 264. no. 5157, pp. 418 - 420
DOI: 10.1126/science.8153629
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Articles

Science, Vol 264, Issue 5157, 418-420
Copyright © 1994 by American Association for the Advancement of Science

articles

Structure of the Tet repressor-tetracycline complex and regulation of antibiotic resistance

W Hinrichs, C Kisker, M Duvel, A Muller, K Tovar, W Hillen, and W Saenger

Institut fur Kristallographie, Freie Universitat Berlin, Germany.

The most frequently occurring resistance of Gram-negative bacteria against tetracyclines is triggered by drug recognition of the Tet repressor. This causes dissociation of the repressor-operator DNA complex and enables expression of the resistance protein TetA, which is responsible for active efflux of tetracycline. The 2.5 angstrom resolution crystal structure of the homodimeric Tet repressor complexed with tetracycline-magnesium reveals detailed drug recognition. The orientation of the operator-binding helix-turn-helix motifs of the repressor is inverted in comparison with other DNA binding proteins. The repressor-drug complex is unable to interact with DNA because the separation of the DNA binding motifs is 5 angstroms wider than usually observed.


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